2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 52(2018) N 3 p. 478-487; DOI 10.1134/S002689331802005X Full Text

D.A. Karasev1,2*, A.V. Veselovsky1, A.A. Lagunin1,2, D.A. Filimonov1, B.N. Sobolev1

Determination of Amino Acid Residues Responsible for Specific Interaction of Protein Kinases with Small Molecule Inhibitors

1Orekhovich Institute of Biomedical Chemistry, Russian Academy of Sciences, Moscow, 119121 Russia
2Pirogov Russian National Research Medical University, Moscow, 117997 Russia

Received - 2016-12-20; Accepted - 2017-05-08

Identifying amino acid positions that determine the specific interaction of proteins with small molecule ligands, is required for search of pharmaceutical targets, drug design, and solution of other biotechnology problems. We studied applicability of an original method SPrOS (specificity projection on sequence) developed to recognize functionally significant positions in amino acid sequences. The method allows residues specific to functional subgroups to be determined within the protein family based on their local surroundings in amino acid sequences. The efficiency of the method has been estimated on the protein kinase family. The residues associated with the protein specificity to inhibitors have been predicted. The results have been verified using 3D structures of protein-ligand complexes. Three small molecule inhibitors have been tested. Residues predicted with SPrOS either in contacted the inhibitor or influenced the conformation of the ligand-binding area. Excluding close homologues from the studied set makes it possible to decrease the number of difficult to interpret positions. The expediency of this procedure was determined by the relationship between an inhibitory spectrum and phylogenic partition. Thus, the method efficiency has been confirmed by matching the prediction results with the protein 3D structures.

protein kinases, small molecule ligands of proteins, protein kinase inhibitors, specific amino acid residues, local sequence similarity